Cellular Processes on a Chip

The Daniel Lab recreates cellular and synthetic processes as organelles-on-a-chip to biomimetically manufacture therapeutic molecules and materials. We do this to understand the biology of posttranslational modifications and coordinate cellular unit operations to define a minimal synthetic cell.

Background: Lipid Rafts

The cell membrane is composed of myriad proteins and biomolecules existing in a patchwork lipid matrix of different phases. This heterogeneity regulates if and when certain species interact. This is done by either sequestering or excluding species from regions of membrane composition until stimuli changes the partitioning preference. Partitioning preference is governed by hydrophobic, electrostatic, and steric forces. It is mediated by the properties of lipids composing the phase. These lipid regions are called microdomains or lipid rafts.

Background: Current Methodologies

Current biochemical methods are inadequate for identifying residents of these regions or monitoring changes between them.

The Daniel Lab Innovations

The Daniel Lab invented an approach which allows control of the spatial and temporal location of different lipid phases within a platform. This allows us to determine when species interact. We do this by combining microfluidic patterning and supported lipid bilayers. Using this technology, we study:
  • Kinetics of phase changes and partitioning.
  • Stimuli which change partitioning of species between phases.
  • How changes in protein-lipid interactions impact protein structure, activity level, and biological function.

What We’re Working On Now

The Daniel Lab pioneered a new method to create supported lipid bilayers manufactured directly from cell plasma membranes. There was no previous way to transport membrane proteins and native lipids to these platforms, while maintaining orientations and not scrambling them between leaflets.

Why this Research Matters

The impact of the newest innovation of the Daniel Lab is twofold.
  • First, detergent reconstitution and associated issues can be avoided.
  • Second, target proteins can be expressed into cells and delivered to the SLB.
Using this approach, we integrate proteinaceous receptors for coronavirus and Ebola into the SLB platform for SPT studies. By expressing viral fusion machinery into cells, we have created a virus-like SLB. The Daniel Lab uses this virus-like SLB to identify anti-fusogenic compounds for enveloped viruses in an HTS manner. We have extended our virus based technology to produce bacteria-like supported bilayers. The Daniel Lab uses the bacteria-like SLBs to examine interactions of anti-bacterial peptides with these surfaces.